mmg_233_2013_genetics_genomicswikiaorg-20200214-history
GWAS: Eye Color
Eye Color Whethere they are deep brown, light blue, awkwardly yellow or a perfect shade of green, eye color is a trait that is affected by many genes throughout the genome. The iris is the structure of the eye that features color and this is determined by a variety of factors including the type, distribution and amount of pigments present. Due to their epigenetic nature and the seemingly endless variety of shades present in humans, this study steps up to the challenge of how to appropriately quantify eye color. Study Set-Up Previous studies have been successful in identifying genetic variants in several genes that are associated with eyecolor, but the methodolgy used was simplified categorical trait information. Participants were broken up into three categories (blue, green or brown) and then an analysis was done to find common SNPs in each phenotype. This study employs the use of high-resolution digital full-eye photographs and analyzes eye color variation through hue and saturation values. High resolution photographs were taken from 5,951 Dutch Europeans and used for further analysis in a genome wide association study. The image on the right shows... "The Hue-Saturation (H-S) eye color space; (B) Example eye photos at their respective position in the H-S space; © 3 color categories defined by an ophthalmologist during eye examination and highlighted in the H-S space; (D) 5 categories defined by two researchers from digital full eye size photographs used for digital quantitative extraction of eye colors; (E) 4 quartiles of the 1st principle component CHS1; and (F) 4 quartiles of the 2nd principle component CHS2; all depicted on the H-S color space" (Digital, 2010) A GWAS was conducted using three independent cohorts and analyzing them for 6 eye color traits. Subjects of non-European descent were excluded from the study. Results Given the large n value a vast number of analysis were done in an attempt to find any significant correlations between eye color and specific areas of the genome. Three new regions, 1q42.3, 17q25.3 and 21q22.13 were isolated and found to be statistically significant for a GWAS. The results that found 17q25.3 and 21q22.13 were later replicated using 2,261 subjects from the UK and 1,282 from Australia. Further analysis was done to determine that the 1q42.3 region likely fell within the LYST gene and the 21q22.13 region likely fell within the DSCR9 gene. The study as a whole showed that using hues and color variation as varaibles is a potentially strong form of analysis. Furthermore the use of digitally quantified results removed human intervention from the equation and likely improved the quality of the results. Works Cited *Digital Quantification of Human Eye Color Highlights Genetic Association of Three New Loci *Fan Liu, Andreas Wollstein, Pirro G. Hysi, Georgina A. Ankra-Badu, Timothy D. Spector, Daniel Park, Gu Zhu, Mats Larsson, David L. Duffy, Grant W. Montgomery, David A. Mackey, Susan Walsh, Oscar Lao, Albert Hofman, Fernando Rivadeneira, Johannes R. Vingerling, André G. Uitterlinden, Nicholas G. Martin, Christopher J. Hammond, Manfred Kayser *PLoS Genet. 2010 May; 6(5): e1000934. Published online 2010 May 6. doi: 10.1371/journal.pgen.1000934